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PubMed2026

Prognostic significance of NLRP-3 expression in solid cancers: a systematic review and meta-analysis.

BACKGROUND: The inflammasome is a critical immunological sensor comprised of NLRP-3, ASC, and CASPASE-1. Mutations in NLRP-3 are prevalent in inflammatory diseases. However, the role of NLRP-3 in cancer is controversial. This study investigates whether NLRP-3 expression is associated with clinical outcomes in patients with solid cancers. METHODS: PubMed (MEDLINE), Embase, Cochrane, and Google Scholar were searched for articles reporting NLRP-3 expression and disease outcome data in cancer patients. RevMan Review Manager was used to calculate pooled hazard ratios and Mantel-Haenszel pooled odds ratios. RNA sequencing datasets from the TCGA Pan-Cancer (PANCAN) were used for external validation. RESULTS: Patients with higher NLRP-3 expression showed a significant association with larger tumor size, advanced tumor grade, TNM stage, and presence of metastasis. High NLRP-3 expression has a significant association with poor OS (HR:2.12, 95% CI = 1.49-3.03), p < 0.0001) and DFS (HR:1.86, 95% CI = 1.30- 2.65, p = 0.0007). Subgroup analysis showed that higher NLRP-3 expression is associated with worse OS in head and neck cancer (HR: 2.77, 95% CI = 1.88-4.09, p < 0.00001), colorectal cancers (HR:2.14, 95% CI= 1.59- 2.87, p < 0.00001), and pancreatic cancer patients (HR: 3.19, 95% CI = 1.73-5.91, p = 0.0002). CONCLUSION: High NLRP-3 expression is associated with advanced disease and poor outcomes in many solid tumours.

Humans↗

PubMed2026

Microbial signal profiles and organism-level concordance between plasma metagenomic sequencing and blood culture in suspected bloodstream infection.

Plasma metagenomic next-generation sequencing (mNGS) and blood culture detect different components of the microbial signal and frequently produce discordant organism reports. We characterized microbial signal class, report-derived burden, organism-level concordance, and independent clinical attribution in a retrospective, single-center, episode-level cohort. Among 329 episodes with evaluable plasma mNGS reports, 315 had blood culture performed; 232 were mNGS positive/culture negative and 53 were positive by both methods. In the 232 discordant episodes, the recorded routine-care diagnosis classified 124 as bloodstream infection (BSI) and 108 as non-BSI. Nonviral signals were present in 78.2% and 42.6%, respectively (P < 0.001), and median maximum report-derived sequence counts were 98.5 and 11.5 (P < 0.001). Two laboratory physicians then independently reviewed source records using structured criteria while masked to the recorded BSI label and mNGS organism and sequence-count information. Initial agreement for the five-category BSI assessment was 97.6% (Cohen's kappa, 0.960). Within the mNGS-positive/culture-negative subgroup, adjudicated BSI likelihood showed a modest ordinal association with report burden (Spearman rho = 0.190; P = 0.004), while mNGS organisms were considered supported in 1 episode, plausible in 158, unlikely or contaminant in 72, and unresolved in 1. Among 53 dual-positive episodes, 33 (62.3%) shared at least one species, but only 5 (9.4%) had complete species-set concordance. Plasma mNGS and blood culture therefore frequently generated non-equivalent organism sets. Signal class and report burden contributed graded contextual evidence, but organism-level attribution required clinical review and orthogonal microbiology rather than binary positivity alone.

Humans↗

PubMed2026

The Efficacy of Erector Spinae Plane Block Versus Subcostal Transversus Abdominis Plane Block in Laparoscopic Nephrectomy: A Randomized Clinical Trial.

OBJECTIVES: This study compared the efficacy and safety of erector spinae plane block (ESPB) versus subcostal transversus abdominis plane (TAP) block in reducing postoperative pain among patients undergoing laparoscopic nephrectomy. METHODS: This randomized clinical trial enrolled 70 adult patients, ASA physical status I or II, who underwent total (radical) laparoscopic nephrectomy under general anesthesia. Patients were randomly assigned to 2 groups. Group ESPB received an ultrasound-guided ESPB at the T7 transverse process level, while group TAP received an ultrasound-guided subcostal TAP block. The primary outcome was the total amount of morphine consumed at 6 and 24 hours postoperatively. Secondary outcomes included the incidence of patients requiring opioid analgesia, time to rescue analgesia, visual analog scale of pain intensity, time to postoperative ambulation, intraoperative and postoperative hemodynamics, arterial partial pressure of oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 or P /F) ratio, and incidence of complications. RESULTS: Compared with the TAP group, the ESPB group exhibited significantly lower median morphine consumption at 24 hours ( P =0.032), prolonged time to first analgesic rescue ( P =0.049), and lower incidence of rescue morphine requirement (OR=0.23; 95% CI=0.06-0.94; P =0.031), with lower visual analog scale pain scores at 12, 18, and 24 hours postoperatively ( P <0.001). The mean arterial blood pressure and heart rates were comparable between groups. No significant adverse effects from either approach. DISCUSSION: In laparoscopic nephrectomy, ultrasound-guided ESPB may safely and effectively be used to improve pain management and reduce pain intensity, with stable hemodynamics and a comparable risk of postoperative complications to the ultrasound-guided subcostal TAP block.

Humans↗

PubMed2026

Unconfined compressive strength prediction for the ordinary Portland cement-steel slag-silica fume ternary system based on response surface methodology.

This research was undertaken to address environmental concerns associated with industrial solid waste and to reduce cement consumption in geotechnical engineering. It specifically investigates the feasibility of using steel slag (SS) and silica fume (SF) as partial substitutes for ordinary Portland cement (OPC) in soil stabilization. The effects of SS, SF, OPC, and initial moisture content on the unconfined compressive strength (UCS) of stabilized soil were investigated through single-factor experiments and response surface methodology (RSM). The results show that SS and SF can synergistically enhance the strength of stabilized soil, although their interaction effect was not statistically significant within the investigated ranges. Compared with soil stabilized solely with OPC, the addition of 18 % SS and 10 % SF reduced OPC consumption by 3 % without compromising strength. Microstructural and compositional analyses further revealed that SS mainly supplied calcium- and silica-bearing components, while SF provided highly reactive silica and micro-filling effects, jointly promoting hydration reactions and improving the compactness of the stabilized soil matrix. As a result, more hydration products were formed in the OPC/SS/SF-stabilized soil than in the OPC-stabilized soil, which contributed to pore filling and strength enhancement. This study provides useful guidance for the sustainable utilization of industrial solid waste and the low-carbon development of soil stabilization materials.

Construction Materials↗

PubMed2025

Elucidation of the immunotoxicity of PEDOT: PSS on RAW264.7 macrophages by oxidative stress, inflammatory response, and NF-κB pathway activation.

Poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT: PSS) nanoparticles, widely used conductive polymers, pose environmental and health risks due to their nanoscale dispersion. However, the characteristics of PEDOT: PSS in aquatic systems and the underlying mechanisms of its toxicity in animal and cell models remain poorly understood. This study aimed to investigate the toxicological effects of PEDOT: PSS nanoparticles on macrophages, with a focus on RAW 264.7 cells. After an acute exposure to PEDOT: PSS nanoparticles at different concentrations (5, 10, 20 μg/mL), we observed significant impairments in cell viability, proliferation, migration, adhesion, and phagocytosis, as well as morphological alterations. Concurrently, there was a marked upregulation of inflammatory markers, including reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β), indicating the induction of oxidative stress and inflammation. Mechanistically, PEDOT: PSS nanoparticles activated the nuclear factor kappa B (NF-κB) signaling pathway, a key regulator of inflammatory responses, suggesting that they may mediate inflammatory responses and cell damage via activation of the NF-κB signaling pathway. These findings reveal the toxic mechanism of PEDOT: PSS nanoparticles in macrophages and provide new insights into their biological safety implications.

Animals↗

PubMed2026

Dynamics and virulence of Enterobacteriaceae reservoirs harboring blaCTX-M group 1 in community wastewater.

UNLABELLED: Extended-spectrum beta-lactamase (ESBL)-producing bacteria are ubiquitous and can cause serious infections. Here, we examined untreated community wastewater influent as a reservoir for blaCTX-M group 1 organisms and their virulence potential. Raw influent samples (n = 268) were collected from four wastewater treatment plants (WWTPs) representing dense urban populations. We observed that blaCTX-M group 1 levels were high at all WWTPs and only ~1-2 log10 lower and not correlated to common human-specific microbiome fecal markers, Lachno3 and HF183, indicating a lack of connection to human fecal inputs. Concentrations of blaCTX-M group 1 genes and markers for presumptive host organisms Escherichia coli and Klebsiella pneumoniae were influenced by travel time and season. Amplicon sequencing revealed high diversity of blaCTX-M group 1-9 genes, with 63% belonging to group 1. Selective culture and 16S rRNA gene sequencing showed blaCTX-M group 1 isolates were 26% E. coli, 26% K. pneumoniae, 40% other Enterobacteriaceae, and 8% Aeromonas. Overall, E. coli averaged 3.6E7 cells/L, with 3% of all E. coli found to contain blaCTX-M group 1. Whole-genome sequencing of blaCTX-M group 1 E. coli from wastewater revealed resistance and virulence gene profiles similar to clinical isolates and distinct from other wastewater ESBL-resistant and non-resistant E. coli. Interpretation of wastewater data needs to consider both the existence of environmental reservoirs that contain potentially pathogenic organisms and the strong influence the dynamics of the conveyance system can have on final concentrations measured at the WWTP. IMPORTANCE: The CTX-M enzyme family is highly abundant in nosocomial, community, and environmental settings and is leading to treatment of infections with carbapenem antibiotics, a last-line therapeutic option. The progressive increase of the clinically relevant blaCTX-M group 1 resistance genes in the human population warrants investigation, particularly to understand the establishment and dynamics of environmental reservoirs. This study utilized molecular and culture methods to gain insight into the possible origin, abundance, and dynamics of blaCTX-M group 1 genes in untreated wastewater influent samples. We found extremely high levels of these genes, with Escherichia coli as a major host organism that closely resembled clinical strains, suggesting they are seeded and propagate in sewer pipe systems. The significance of our research is in developing approaches to monitor antimicrobial resistance reservoirs in community wastewater, which could shed light on global burdens and potential transmission cycles and indicate increasing inputs of clinically relevant strains originating from human populations.

E. coli↗

PubMed2026

An RPA-assisted homogeneous electrochemical DNA sensor for on-site eDNA detection toward early warning of crown-of-thorns starfish outbreaks.

Crown-of-thorns starfish (COTS) outbreaks seriously threaten coral reef ecosystems, while conventional monitoring approaches are time-consuming and often lack sufficient sensitivity for early warning. Existing electrochemical DNA sensors usually require complex electrode-surface immobilization procedures, which can lead to uneven probe distribution, significant steric hindrance, and poor stability. Meanwhile, the low concentration of environmental DNA (eDNA) in marine environments further complicates detection. To overcome these challenges, this study developed a homogeneous electrochemical DNA sensor assisted by recombinase polymerase amplification (RPA) for COTS eDNA detection. Target DNA was first amplified by RPA, and the amplification products were then hybridized in solution with capture probe (CP)-modified magnetic beads (MB) and biotin-labeled signal probe (SP) to form sandwich-structured MB complexes. These complexes were subsequently magnetically enriched and immobilized on the electrode surface for electrochemical signal readout. Under optimized conditions, the sensor displayed a linear response to COTS genomic DNA from 3.77 fg/μL to 1 ng/μL, with an LOD of 2.02 fg/μL and an LOQ of 3.77 fg/μL. The sensor was applied to Xisha Islands samples, and the results agreed with droplet digital PCR (ddPCR) (P > 0.05), demonstrating its potential for sensitive and reliable on-site COTS eDNA detection.

Animals↗

PubMed2026

Electron shuttles facilitate methane-dependent arsenate reduction in paddy soils.

Methane-dependent arsenate reduction (M-AsR) occurs widely in paddy soils and can substantially enhance arsenic mobilization, posing potential ecological risks. However, the role of electron shuttles in this process remains poorly understood. In this study, we investigated the influence of anthraquinone-2,6-disulfonate (AQDS) on M-AsR in paddy soils. Fourteen-day incubation showed that 1 mmol/L AQDS facilitated 50.88 % of arsenate reduction and 31.31 % of methane oxidation. Quantitative polymerase chain reaction analysis revealed that AQDS significantly increased the abundance of functional genes associated with arsenate reduction (arrA, arsC) and anaerobic methane oxidation (mcrA) (P < 0.05). Microbial community analysis revealed that AQDS addition enriched Cloacibacterium, Sphingorhabdus, and Methylocystis, while decreasing the relative abundance of Methylobacter and Methylomonas. These findings indicate that electron shuttles facilitate M-AsR by modulating functional microbial populations, providing valuable insights into arsenic biogeochemistry and the coupled cycling of methane and arsenic in paddy soils.

Methane↗

PubMed2026

Ablative radiotherapy in castration-resistant prostate cancer.

OBJECTIVE: To prove the oncological benefit of ablative radiotherapy in patients with up to five metastases from castration-resistant prostate cancer (CRPC) a single-centre randomised trial was initiated. PATIENTS AND METHODS: This monocentric, randomised, phase II clinical trial enrolled patients with up to five prostate-specific membrane antigen-positive bone or lymph node metastases developing prostate-specific antigen (PSA) progression during androgen deprivation (ADT) or ADT and androgen-receptor targeted therapy. Participants were randomised (2:1) to receive metastasis-directed therapy (MDT) or observation (OBS) without changing systemic therapy. The primary endpoint was the proportion of patients having PSA progression within 1 year, with statistical analyses conducted using intention-to-treat principles. Here, results of a planned interim analysis of the primary endpoint are reported. RESULTS: A total of 30 patients (12 in the observation arm and 18 in the MDT arm) were enrolled, PSA progression within 1 year occurred in 44% of the MDT group vs 75% in the OBS group (P = 0.14, not significant). The median time to PSA progression was significantly longer in the MDT arm (12.4 months) compared to the OBS arm (2.9 months, P = 0.03). The pre-defined criteria to discontinue the study were not met. Limitations include the single-centre design and small sample size at interim analysis. CONCLUSION: This pre-planned interim analysis of the primary endpoint did not meet the discontinuation criteria of the study protocol, suggesting that MDT in oligometastatic CRPC may extend the time to PSA progression without immediate change of systemic therapy. The continuation of the study in a multicentre setting is planned (Institutional funding by the TU Dresden, ClinicalTrials.gov identifier: NCT04141709).

Humans↗

PubMed2026

Addition of High-Dose Vitamin D3 to Standard Treatment in Patients With Metastatic Colorectal Cancer: The SOLARIS Randomized Clinical Trial (Alliance A021703).

IMPORTANCE: In a phase 2 randomized clinical trial, high-dose vitamin D3 added to standard treatment improved progression-free survival (PFS) compared with standard-dose vitamin D3 in patients with metastatic colorectal cancer (mCRC). OBJECTIVE: To determine if high-dose vitamin D3 added to standard chemotherapy improves outcomes in patients with previously untreated mCRC. DESIGN, SETTING, AND PARTICIPANTS: Double-blind phase 3 randomized clinical trial enrolling 455 patients with previously untreated mCRC, conducted in the US through the National Clinical Trials Network from October 2019 to December 2022 (database freeze: July 15, 2024). INTERVENTIONS: mFOLFOX6 (modified FOLFOX6 [5-fluorouracil, leucovorin, oxaliplatin]) or FOLFIRI (5-fluorouracil, leucovorin, irinotecan) plus bevacizumab every 2 weeks with either high-dose vitamin D3 (8000 IU daily × 14 days as loading dose followed by 4000 IU daily) or standard-dose vitamin D3 (400 IU daily) until disease progression, intolerable toxicity, or withdrawal of consent. MAIN OUTCOMES AND MEASURES: The primary end point was PFS assessed by the unstratified log-rank test. Secondary end points included objective response rate, overall survival, and toxicity. Prespecified subgroup analyses of PFS were performed according to known prognostic factors. RESULTS: Among 455 randomized patients (median age, 59 years; 181 [40%] female) with median follow-up 20 months, the median PFS for high-dose vitamin D3 (n = 228) was 11.8 months (95% CI, 10.3-13.3) vs 10.3 months (95% CI, 9.4-12.2) for standard-dose vitamin D3 (n = 227) (1-sided log-rank P = .25). There were no significant differences in objective response rate between high-dose and standard-dose vitamin D3 (51% [95% CI, 44%-58%] vs 44% [95% CI, 37%-50%], respectively; P = .12), or in overall survival (median, 25.6 vs 27.0 months; 1-sided log-rank P = .66). There were no clinically meaningful differences in the most common grade 3 or greater adverse events between the high- and standard-dose groups, including neutropenia (n = 67 [32%] vs n = 62 [30%]) and hypertension (n = 42 [20%] vs n = 49 [23%]) or in incidence of vitamin D-associated toxicities. CONCLUSIONS AND RELEVANCE: Among patients with previously untreated mCRC, addition of high-dose vitamin D3, vs standard-dose vitamin D3, to standard chemotherapy plus bevacizumab did not improve PFS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04094688.

Aged↗

PubMed2026

Medically Unexplained Symptoms: A Systematic Umbrella Review of Current Terminology and Reported Rationales.

OBJECTIVES: Toaddress current naming conventions for Medically Unexplained Symptoms (MUS) through a systematic umbrella review. The terminology used and the provided rationales were considered. METHODS: Registered with PROSPERO (CRD42024526020), this review searched 8 key databases, last on January 28, 2025. Reviews including medically unexplained symptoms (or synonym or subtype) in their systematic search terms were included (N=422). RESULTS: A total of 577 references to 111 terms were made across the reviews, with numerous reviews using the same overarching terms, including "functional" (n=233), "somatic" (or variants thereof, n=51), and "medically unexplained" (n=28). Thirty percent of terms (n=179) were to specific syndromes or terms that did not group together under an overarching term, suggesting substantial variability in terms, even though over 60% of authors were primarily associated with just 3 disciplines: medicine, allied health, and psychology. A subset of 23 reviews provided rationales, which were subjected to content analysis and a ROBIS (Risk of Bias in Systematic Reviews) risk-of-bias assessment. This analysis showed that rationales tended to (1) highlight differences between psychological, psychiatric, and other medical fields (n=7); (2) focus on the patient perspective and patient-practitioner therapeutic relationship (n=10); or (3) follow broad and/or commonly used terms (n=7). DISCUSSION: The current landscape of terminology used for MUS remains varied, nuanced, and inconsistent between disciplines. Moving forward to a more universal language accepted and used by both patients and practitioners would aid in the diagnosis, management, and treatment of MUS.

Humans↗

PubMed2026

Systematic review of microorganism disinfection performance by chemical and ultraviolet light water treatment methods.

Safe drinking water is critical for public health, yet microbial contamination remains a significant global challenge. We conducted a systematic review to update World Health Organization guidance on water disinfection technologies by synthesizing peer-reviewed literature from 1997 to 2021 on the performance of free chlorine, chlorine dioxide, ozone, and ultraviolet (UV) light against bacteria, viruses, and protozoa. Following PRISMA guidelines, we analyzed log10 reduction values (LRVs) and contact times (Ct) or fluence (for UV) from laboratory and field studies. We included studies from multiple databases and expert-recommended studies. Results show mean Cts for 2 LRV of non-opportunistic bacteria as 6.0 (free chlorine), 0.4 (chlorine dioxide), and 1.2 (ozone) mg/L*min, and a mean UV fluence of 8.2 mJ/cm² (all bacteria). Viruses required lower Cts, except for UV-resistant adenoviruses, while protozoa required higher Cts or fluences. Opportunistic bacteria required significantly higher Cts than non-opportunistic bacteria for free chlorine and chlorine dioxide. Temperature and pH effects were inconsistent, highlighting data variability and gaps in field studies. These findings support global guidance on water treatment and may be used alongside other context-specific data to understand the roles these technologies play in reducing waterborne exposures. We recommend standardized reporting from performance studies to enable straightforward synthesis of evidence.

Disinfection↗

PubMed2026

Diving Deeper Into Mechanisms of Acrylamide-Induced Toxicity: RNA Sequencing Reveals Transcriptomic Alteration and Retrotransposon Expression in Drosophila melanogaster.

Given the inevitability of human and animal exposure to acrylamide, there is increasing concern regarding its potential health risks. While a number of molecular mechanisms have been proposed, the complexity of acrylamide toxicological pathways and interactions remains incompletely characterized. In this study, we employed a transcriptomic approach to investigate the transcriptional responses of Drosophila melanogaster following exposure to acrylamide (100 mg/kg). Our analysis identified 634 differentially expressed genes (DEGs), with 362 upregulated and 272 downregulated. Functional analysis revealed these DEGs are enriched in pathways related to reproduction, detoxification, cellular and metabolic processes, signaling, synaptic formation and organization. Notably, acrylamide exposure upregulated the expression of tau and beta-amyloid protein precursor-like genes, both implicated in Alzheimer's disease pathology. An aversive memory test further demonstrated that acrylamide impaired the short-term memory of treated flies. Additionally, acrylamide-induced toxicity altered the expression of nine long terminal repeat retrotransposons, belonging to the gypsy and pao superfamilies. By exploring the potential role of transposable element activity in acrylamide-mediated toxicity, this study provides novel insights into the molecular mechanisms underlying its effects. Collectively, these findings offer a more comprehensive understanding of the mechanisms and pathways associated with the toxic action and detoxification of acrylamide in D. melanogaster.

Animals↗

PubMed2026

Are there any common effects in preclinical models of micro- and nanoplastic (MNP) exposure? A systematic review.

Micro- and nanoplastics (MNPs) are emerging contaminants detected in food sources and the marine food chain, raising concerns about human health. Although no causal relationship has been established between MNP exposure and specific diseases, growing evidence suggests adverse developmental, behavioral, cognitive and biochemical effects. This systematic review synthesized evidence from common preclinical neurotoxicology models, including C. elegans, D. rerio, D. melanogaster, in vitro systems and rodents, to identify convergent developmental, behavioral and biochemical outcomes. The protocol was preregistered in OSF, followed PRISMA-P guidelines, applied PICOS criteria, and assessed methodological quality using the European Commission's ToxRTool. Overall, 185 studies were included. Consistent findings showed impaired survival and disrupted development across all models. Behavioral alterations affecting anxiety, memory, learning, sociability and locomotor activity were also consistently reported. In addition, numerous studies identified disruptions in the serotonergic (5-HT) system, including changes in neurotransmitter levels, transporters and metabolic enzymes. Despite methodological heterogeneity, these findings indicate that MNP exposure produces reproducible neurodevelopmental and neurochemical alterations across experimental models. Future studies should improve methodological harmonization, strengthen cross-model comparability and identify robust biomarkers and key mechanisms underlying MNP-induced neurotoxicity, facilitating translation to human health risk assessment frameworks.

Animals↗

PubMed2026

Prenatal exposure to particulate matter (PM) and autism spectrum disorder (ASD) among children: a systematic review and meta-analysis.

The global surge in Autism Spectrum Disorder (ASD) cases, coupled with evidence linking prenatal Particulate Matter (PM) exposure to developmental disruption, demands a comprehensive review to design targeted health interventions. This systematic review and meta-analysis aim to evaluate the strength and consistency of evidence linking prenatal PM exposure to ASD across studies, quantifying this relation to identify actionable environmental risk thresholds. This study employed PRISMA protocols to systematically extract and evaluate evidence from PubMed, Web of Science, Scopus, and ScienceDirect (2010-2024), and screened 4,013 articles to identify qualified case-control and cohort studies (n=29). Data synthesis employed random-effects modeling, accompanied by comprehensive assessment through I2 statistics, Q-tests, funnel plots, Duval and Tweedie's trim-and-fill analysis, and Egger's regression, to ensure validity. A meta-analysis of 16 case-control studies revealed a 34 % increased risk of ASD associated with prenatal PM exposure (pooled OR=1.34; 95 % CI: 1.13-1.54), despite substantial between-study heterogeneity (I2=94.02 %, p<0.001). Publication bias was not significant (Egger's test p value=0.114). Critical trimester-specific analysis uncovered that third-trimester exposure significantly increased ASD risk (OR=1.17; 95 % CI: 1.01-1.34), while first-trimester (OR=1.02; 95 % CI: 0.92-1.11; I2=49.18 %, p<0.10) and second-trimester exposures (OR=1.13; 95 % CI: 0.88-1.38; I2=92.59 %, p<0.001) showed non-significant associations. This review identified prenatal and early life exposure to PM as a risk factor for ASD, indicating a trimester-specific vulnerability. It highlighted the necessity of focused air quality interventions and targeted guidance to reduce prenatal PM exposure to alleviate ASD risk during the critical-window.

Child↗

PubMed2026

Comparative analysis of genomic variations among different Cdo1 paralogs for salinity-adaptation in oysters.

Under rapid climate change and anthropogenic activities, oysters, a global aquaculture species, are subjected to exacerbated culturing environments, especially for those living in in-shore estuarine species, such as Suminoe oysters Crassostrea ariakensis. This study aims to investigate the molecular mechanisms of salinity adaptation of C. ariakensis. We performed an expression genome-wide association study (eGWAS) to compare genetic regulation among 5 paralogous copies of a key salinity-related gene, cysteine dioxygenase 1 (Cdo1). A total of 40 significant eSNPs with 82 adjacent eGenes were identified in 2 copies (Cdo1_26639 and Cdo1_1666). We identified only trans-eSNPs for Cdo1_26639 and more cis-eSNPs for Cdo1_1666, and different eGenes for these 2 Cdo1 copies, which indicated that the expressional regulation of these paralogs may undergo distinct pathways. We identified 3 eGenes that exhibited identical expression patterns with Cdo1_26639 and Cdo1_1666, including 6-Pgdh, Trapp and tandem copy of Cdo1_27337. The expression correlation between Cdo1 copies and eGenes was enhanced under salinity stresses, suggesting the crucial role of eGenes in regulating Cdo1's expression in response to salinity changes. Our results provide comprehensive identification and comparison of eSNPs across different paralogous copies of one gene, along with insights into the molecular mechanisms underlying salinity tolerance, and genetic markers for breeding salinity-resistant oysters.

Animals↗

PubMed2026

Modulation of heart rate and heart rate variability during animal-assisted treatment of patients in a minimally conscious state: A randomized controlled crossover study.

BACKGROUND: Animal-assisted treatment (AATx) is a promising and increasingly used approach in neurorehabilitation, yet its psychophysiological effects remain largely unexplored. Patients in a minimally conscious state (MCS) show severely altered consciousness with minimal but definite behavioral signs of awareness. Because behavioral assessment in this population is limited, psychophysiological measures such as heart rate (HR) and heart rate variability (HRV) may offer valuable insights into autonomic regulation during therapy. AIM: The present study investigated whether AATx influences HR and HRV compared to treatment as usual (TAU). METHODS: A randomized controlled crossover design with repeated measures was conducted. HR and HRV data were recorded using an Empatica E4 wristband, and linear mixed-effects models were fitted for each outcome variable. The analytic sample included twenty-one patients with MCS who completed at least one of the four sessions. RESULTS: We found a significant decrease in mean HR (estimate = -12.75, p = .041) and a significant increase in the standard deviation of normal-to-normal intervals (SDNN) (estimate = 15.76, p = .020) during AATx compared to TAU from the pretreatment to the posttreatment phase, indicating enhanced parasympathetic activation and greater autonomic flexibility. Other HRV parameters revealed no significant effects of AATx, though trends were consistent with the hypotheses. CONCLUSIONS: These findings provide preliminary physiological evidence that AATx can modulate autonomic activity in MCS patients. Despite limitations related to sample size and recording quality, the results highlight the potential of AATx as an emotionally engaging intervention in early neurorehabilitation.

Humans↗

PubMed2026

Ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated non-small-cell lung cancer after disease progression on EGFR tyrosine kinase inhibitor therapy (HARMONi): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: Ivonescimab has shown clinical efficacy in non-small-cell lung cancer (NSCLC). We aimed to assess the efficacy and safety of ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated NSCLC whose disease progressed after third-generation EGFR tyrosine kinase inhibitor (TKI) therapy. METHODS: HARMONi is a randomised, placebo-controlled, double-blind, phase 3 trial done at 114 cancer centres and hospitals across Asia, Europe, and North America. Eligible patients were aged at least 18 years (upper limit: 75 years in Asia) with stage IIIB/IIIC or IV non-squamous EGFR-mutated NSCLC, disease progression after treatment with a third-generation EGFR-TKI, and an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were randomly assigned (1:1) via a centralised interactive voice response system or interactive web response system to receive ivonescimab (20 mg/kg) or placebo plus pemetrexed (500 mg/m2) and carboplatin (target area under the curve 5 mg/mL per min) intravenously every 3 weeks. Randomisation was stratified by brain metastases status at enrolment and geographical region. The primary endpoints were progression-free survival by blinded independent radiology review committee and overall survival in the intention-to-treat population. Safety was assessed in patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov (NCT06396065), has completed enrolment, and is ongoing for treatment and follow-up. FINDINGS: From Jan 25, 2022, to Oct 1, 2024, 660 individuals were screened for eligibility; of these, 438 were enrolled and randomly assigned to receive ivonescimab plus chemotherapy or placebo plus chemotherapy (219 per group). Of enrolled patients, 257 (59%) were female and 181 (41%) were male; 306 (70%) reported race as Asian, and 105 (24%) as White. At a median follow-up of 22·3 months (95% CI 21·5-23·0), 275 progression or death events had occurred in 345 patients (129 events among 172 patients in the ivonescimab plus chemotherapy group and 146 events among 173 patients in the placebo plus chemotherapy group). Median progression-free survival was 6·8 months (95% CI 5·7-7·1) in the ivonescimab plus chemotherapy group versus 4·4 months (4·1-5·5) in the placebo plus chemotherapy group (hazard ratio [HR] 0·52; 95% CI 0·41-0·66; p<0·0001). At a median follow-up of 29·7 months (95% CI 27·7-31·0), 262 deaths occurred in 438 patients (122 in the ivonescimab plus chemotherapy group and 140 in the placebo plus chemotherapy group). Median overall survival was 16·8 months (14·3-19·0) in the ivonescimab plus chemotherapy group versus 14·0 months (12·8-15·7) in the placebo plus chemotherapy group (HR 0·79; 0·62-1·01). The most common grade 3-4 treatment-related adverse events in the ivonescimab plus chemotherapy versus the placebo plus chemotherapy group were decreased neutrophil count (42 [19%] of 218 vs 36 [17%] of 218), decreased white blood cell count (28 [13%] vs 24 [11%]), decreased platelet count (27 [12%] vs 14 [6%]), and anaemia (22 [10%] vs 27 [12%]). Serious treatment-related adverse events occurred in 61 (28%) patients in the ivonescimab plus chemotherapy group and 33 (15%) patients in the placebo plus chemotherapy group. Treatment-related adverse events led to death in four patients (disease progression, multiple organ dysfunction syndrome, and hepatic failure, each in one patient; gastrointestinal haemorrhage and pulmonary embolism in one patient) in the ivonescimab plus chemotherapy group and five patients (pneumonitis, myocardial infarction, cerebrovascular accident, cognitive disorder, and embolic stroke, each in one patient) in the placebo plus chemotherapy group. INTERPRETATION: Ivonescimab plus chemotherapy showed a clinically meaningful and statistically significant progression-free survival benefit in patients with EGFR-mutated NSCLC after progression on EGFR-TKI therapy. The clinical benefit and lack of new safety signals of ivonescimab with chemotherapy support the potential for the combination as a new treatment option in this patient population. FUNDING: Summit Therapeutics.

Humans↗